Am. J. Respir. Cell Mol. Biol., Volume 20, Number 3, March, 1999 465-473

Pertussis Toxin-Induced Lung Edema
Role of Manganese Superoxide Dismutase and Protein Kinase C

Min-Fu Tsan, Xiaomin Cao, Julie E. White, Joseph Sacco, and C. Y. Lee

Research, Medical, and Laboratory Services, Samuel S. Stratton Department of Veterans Affairs Medical Center; and Departments of Physiology, Medicine, and Pathology and Laboratory Medicine, Albany Medical College, Albany, New York

The mechanism by which pertussis toxin (Ptx) causes lung edema is not clear. We investigated the role of pulmonary manganese superoxide dismutase (MnSOD) and protein kinase C (PKC) in Ptx-induced lung edema. We demonstrated that intraperitoneal injection of Ptx at a concentration of 5 µg/100 g body weight caused a similar degree of lung edema in 2 d, as measured by lung wet weight/dry weight ratio, in heterozygous MnSOD gene (Sod2)-knockout mice (Sod2^+/) and in their wild-type littermates (Sod2^+/+). The level of lung MnSOD activity in Sod2^+/ mice was approximately half that of Sod2^+/ mice. Ptx had no effect on levels of lung MnSOD messenger RNA, immunoreactive protein, or enzyme activity in either Sod2^+/+ or Sod2^+/ mice. Ptx also had no effect on lung copper-zinc SOD, catalase, and glutathione peroxidase activities in these mice. On the other hand, Ptx caused the activation of lung PKC, for example, by translocation of a 72-kD PKC isoform from the cytosolic fraction to the membrane fraction. Pretreatment of mice with bisindolylmaleimide, a PKC inhibitor, prevented both the Ptx-induced activation of PKC and lung edema. These data suggest that Ptx-induced lung edema in mice is, at least in part, due to the activation of lung PKC.

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